Granted Patent
B2
US 12,653,913 · App. 18/119,070 · Granted Jun 16, 2026
HER2 binders
Inventors:
Faisal Ahmed Syud (Clifton Park, NY); Brian Duh-Lan Lee (Rexford, NY); Rong Zhang (Niskayuna, NY); Peter Brian Iveson (Amersham, GB); Paul Schaffer (Vancouver, CA); Tove Simonsson (Lund, SE); Elin Gunneriusson (Saltsjobaden, SE); Fredrik Frejd (Stockholm, SE); Lars Abrahmsen (Valhallavagen, SE); Joachim Feldwisch (Tyreso, SE); Nina Herne (Stockholm, SE); Christofer Lendel (Farsta, SE)
View Patent ↗
Loading inventors, assignments & file history…
Abstract
Imaging agents comprising an isolated polypeptide conjugated with a radionucleide and a chelator; wherein the isolated polypeptide binds specifically to HER2, or a variant thereof; and methods for preparing and using these imaging agents.
Claims (16)
1 . A method of imaging at least a portion of a subject comprising:
administering a composition to the subject, wherein the composition comprises an isolated polypeptide conjugated with a 18 F via an aminoxy linker,
wherein the aminoxy linker is
wherein the isolated polypeptide comprises SEQ ID No: 1 or SEQ ID No: 2, and wherein the isolated polypeptide binds specifically to HER2; and
imaging a portion of the subject with a PET device.
2 . The method of claim 1 , further comprising the step of diagnosing the subject with a HER2 expressing cancer when the imaged portion shows over-expression of HER2.
3 . The method of claim 2 , wherein the HER2 expressing cancer is breast cancer.
4 . The method of claim 1 , wherein the 18 F is conjugated to the isolated polypeptide via the aminoxy linker at the N-terminus of the isolated polypeptide.
5 . The method of claim 1 , further comprising the step of monitoring delivery of the composition to the subject by imaging the subject during administration of the composition using the PET device.
6 . A method of imaging at least a portion of a subject comprising:
administering a composition to the subject, wherein the composition comprises an isolated polypeptide comprising SEQ ID No: 2 conjugated with a 18 F via a linker, wherein the linker is
wherein the isolated polypeptide binds specifically to HER2; and
imaging the subject with a PET device.
7 . The method of claim 6 , further comprising the step of diagnosing the subject with a HER2 expressing cancer, when the imaged subject shows over-expression of HER2.
8 . The method of claim 7 , wherein the HER2 expressing cancer is breast cancer.
9 . The method of claim 6 , further comprising the step of monitoring delivery of the composition to the subject by imaging the subject during administration of the composition using the PET device.
Assignments (3)
NUNC PRO TUNC ASSIGNMENT
Recorded Oct 12, 2025
From: GENERAL ELECTRIC COMPANY
To: GE PRECISION HEALTHCARE LLC
Reel/Frame 072543/0278 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 23, 2023
From: SIMONSSON, TOVE; GUNNERIUSSON, ELIN; FREJD, FREDRIK; ABRAHMSEN, LARS; FELDWISCH, JOACHIM; HERNE, NINA; LENDEL, CHRISTOFER
To: AFFIBODY AB
Reel/Frame 063153/0638 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 23, 2023
From: SYUD, FAISAL AHMED; LEE, BRIAN DUH-LAN; ZHANG, RONG; IVESON, PETER BRIAN; SCHAFFER, PAUL
To: GENERAL ELECTRIC COMPANY
Reel/Frame 063153/0773 →
Continuity (5)
References Cited (142)
US 7597876B2
· McBride et al.
· 2009
[cited by applicant]
US 7902332B2
· Jesus et al.
· 2011
[cited by applicant]
US 7993650B2
· Carlsson et al.
· 2011
[cited by applicant]
US 8426557B2
· Bergman et al.
· 2013
[cited by applicant]
US 8487080B2
· Jesus et al.
· 2013
[cited by applicant]
US 8501909B2
· Abrahmsén et al.
· 2013
[cited by applicant]
US 8883120B2
· Abrahmsén et al.
· 2014
[cited by applicant]
US 9061080B2
· Hiscock
· 2015
[cited by examiner]
US 9175067B2
· Abrahmsen
· 2015
[cited by applicant]
US 9187535B2
· Lindborg et al.
· 2015
[cited by applicant]
US 9211344B2
· Ekblad et al.
· 2015
[cited by applicant]
US 9238810B2
· Jarstad et al.
· 2016
[cited by applicant]
US 9469670B2
· Abrahmsén et al.
· 2016
[cited by applicant]
US 20160303262A1
· Engell et al.
· 2016
[cited by applicant]
EP 2077272A1
· 2009
[cited by applicant]
JP 2007015993A
· 2007
[cited by applicant]
WO 199101743A1
· 1991
[cited by applicant]
WO 199200091A1
· 1992
[cited by applicant]
WO 199519374A1
· 1995
[cited by applicant]
WO 2004037297A1
· 2004
[cited by applicant]
WO 2004080492A1
· 2004
[cited by applicant]
WO 2005000883A1
· 2005
[cited by applicant]
WO 2005003156A1
· 2005
[cited by applicant]
WO 2005003456A1
· 2005
[cited by applicant]
WO 2005075507A1
· 2005
[cited by applicant]
WO 2005097202A2
· 2005
[cited by applicant]
WO 2006067376A2
· 2006
[cited by applicant]
WO 2006092338A2
· 2006
[cited by applicant]
WO 2007065635A1
· 2007
[cited by applicant]
WO 2008049866A1
· 2008
[cited by applicant]
WO 2008118601A2
· 2008
[cited by applicant]
WO 2009077175A1
· 2009
[cited by applicant]
WO 2009077569A1
· 2009
[cited by applicant]
WO 2009080810A1
· 2009
[cited by applicant]
WO 2009080811A1
· 2009
[cited by applicant]
WO 2009135015A2
· 2009
[cited by applicant]
WO 2010079079A2
· 2010
[cited by applicant]
WO 2012087908A1
· 2012
[cited by applicant]
WO 2012087912A1
· 2012
[cited by applicant]
Ahlgren et al., “Evaluation of Maleimide Derivative of DOTA for Site-Specific Labeling of Recombinant Affibody Molecules,” Bioconjugate Chem., vol. No. 19, pp. 235-243, 2008.
[cited by applicant]
Alberto et al., “Synthesis and Properties of Boranocarbonate: A Convenient in Situ CO Source for the Aqueous Preparation of [99mTc(OH2)3(CO)3]+”, J. Am. Chem. Soc., vol. No. 123, Issue No. 13, pp. 3135-3136, 2001.
[cited by applicant]
Anna Orlova et al.; “Synthetic Athbody Molecules: A Novel class of Affinity Ligands for Molecular Imaging of HER2-Expressing Malignant Tumors”; Cancer Res 2007; 67; Published online Mar. 1, 2007; p. 2178-2186.
[cited by applicant]
Anna Orlova et al; “Comparative In Vivo Evaluation of Technetium and lodine Labels on an Anti-HER2 Affibody for Single Photon Imaging of HER2 Expression in Tumors”; J. Nuc. Med. 2006, 47, pp. 512-519.
[cited by applicant]
Ann-Charlott Steffen et al.; “In Vitro Characterization of a Bivalent Anti-HER-2 Affibody with Potential for Radionuclide-Based Diagnostics”; vol. 20, No. 3, 2005; pp. 239-248.
[cited by applicant]
Baum, et al., “Molecular Imaging of HER2—Expressing Malignant Tumors in Breast Cancer Patients Using Synthetic 111In- or 68Ga-Labeled Affibody Molecules,” The Journal of Nuclear Medicine, vol. 51, No. 6, Jun. 2010, 6 pa…
[cited by applicant]
Bruskin et al., “Radiobromination of monoclonal antibody using potassium [76Br] (4 isothiocyanatobenzyl-ammonio)-promo-decahydro-closo-dodecaborate (Bromo-DABI)”, Nuclear Medicine and Biology, vol. No. 31, pp. 205-211, …
[cited by applicant]
Cai et al, J. Nucl. Med., vol. 47, pp. 1172-1180 (Year: 2006).
[cited by applicant]
Cai et al., “A Thiol-Reactive 18F-Labeling Agent, N-[2-{4-18F-Fluorobenzamido) Ethyl]Maleimide, and Synthesis of RGD Peptide-Based Tracer for PET Imaging of avβ3 Integrin Expression”, The Journal of Nuclear Medicine, vo…
[cited by applicant]
Cheng et al., Small-Animal PET Imaging of Human Epidermal Growth Factor Receptor Type 2 Expression with Site-Specific 18F-Labeled Protein Scaffold Molecules, The Journal of Nuclear Medicine, vol. No. 49, Issue No. 5, Ma…
[cited by applicant]
Communication under Rule 71(3) EPC, European Patent Office received in Application No. 11 804 895.8-1109 dated Mar. 5, 2021, 66 pages. Not Sure This is Prior Art.
[cited by applicant]
Cooper et al., “Conjugation of chelating agents to proteins and radiolabeling with trivalent metallic isotopes”, Nature Protocols, vol. No. 1, Issue No. 1, pp. 314-317, 2006.
[cited by applicant]
Cowan et al., “Hydrophobicity Indices for Amino Acid Residues as Determined by High-Performance Liquid Chromatography”, Peptide Research, vol. 3, No. 2, pp. 75-80, 1990.
[cited by applicant]
Cyer et al, Inorg. Chem., 2001, vol. 40, No. 14, pp. 3555-3651.
[cited by applicant]
Dale O. Kiesewetter et al; “Radiolabeling of HER2-specific Affibody® molecule with F-18”; Journal of Fluorine chemistry 129(2008); Available online Jul. 1, 2008; doi. 10.1016/j.jfluchem.2008.06.021; pp. 799-806.
[cited by applicant]
Darter, “Improving the Efficacy of Antibody-based Cancer Therapies”, vol. No. 1, pp. 118-129, Nov. 2001.
[cited by applicant]
Drlova et al., “Pre-clinical evaluation of [111 In]-benzyl-DOT A-ZH ER2:342, a potential agent for imaging of HER2 expression in malignant tumors”, International Journal of Molecular Medicine, vol. No. 20, pp. 697-404, …
[cited by applicant]
Duibell et al., “Fmoc Solid Phase Peptide Synthesis—A Practical Approach”, pp. 115-135, 2000.
[cited by applicant]
Eigenbrot et al., “Structural basis for high-affinity HER2 receptor binding by an engineered protein”, PNAS, vol. No. 107, Issue No. 34, pp. 15039-15044, Aug. 24, 2010.
[cited by applicant]
Eisenwiener et al., A Convenient Synthesis of Novel Bifunctional Prochelators for Coupling to Bioactive Peptides for Radiometal Labelling, Bioorganic & Medicinal Chemistry Letters, vol. 10, pp. 2133-2135, 2000.
[cited by applicant]
Ekman et al., “Activation of Growth Factor Receptors in Esophageal Cancer-Implications for Therapy”, The Oncologist, vol. No. 12, pp. 1165-1177, 2007.
[cited by applicant]
European Search Report and Written Opinion issued in connection with related EP Application No. 17150395.7-2406 dated Aug. 6, 2008.
[cited by applicant]
Extended European Search Report received in Application No. 21190695.3-1109, dated Dec. 1, 2021, 16 pages.
[cited by applicant]
Feldwisch et al., “Clinical and Pre-clinical Application of HER2-Specific Affibody Molecules for Diagnosis of Recurrent HER2 Positive Breast Cancer by SPECT or PET/CT”, Abstracts, Molecular Imaging, vol. No. 5, Issue No…
[cited by applicant]
Final Rejection towards related U.S. Appl. No. 13/996,142 dated Dec. 4, 2015.
[cited by applicant]
Goldenberg, “Targeted Therapy of Cancer with Radiolabeled Antibodies”, Radioimmunotherapy of Dancer, The Journal of Nuclear Medicine, vol. No. 43, Issue No. 5, pp. 693-713, May 2002.
[cited by applicant]
Greenlee et al.,Cancer Statistics, CA Cancer J Clin 2001, vol. No. 51, Issue No. 1, pp. 15-36, Jan./Feb. 2001.
[cited by applicant]
Haack et al., “Serine Derived Oxazolidines As Secondary Structure Disrupting, Solubilizing Building Blocks In Peptide Synthesis”, Tetrahedron Letters, vol. 33, No. 12, pp. 1589-1592, 1992.
[cited by applicant]
Heskamp et al., “Imaging of human epidermal growth factor receptor type 2 expression with 1 BF-labeled affibody molecule ZHER2:2395 in a mouse model for ovarian cancer”, The Journal of Nuclear Medicine, vol. 53, No. 1. …
[cited by applicant]
Hofström, et al., “Use of a HEHEHE Purification Tag Instead of Hexahistidine Tag Improves Biodistribution of Affibody Molecules Site-Specifically Labeled with 99mTc, 111In, and 125I,” Journal of Medicinal Chemistry, Apr…
[cited by applicant]
Holbro et al., “ERBB Receptors: Directing Key Signaling Networks Throughout Life”, Annu. Rev. Pharmacol. Toxicol., vol. No. 44, pp. 195-217, 2004.
[cited by applicant]
Hynes et al., “The biology of erbB-2/neu/HER-2 and its role in cancer”, Biochimica et Biophysica Acta, vol. No. 1198, pp. 165-184, 1994.
[cited by applicant]
International Search Report and Written Opinion corresponding lo PCT Application No. PCT/US2011/065794, dated Mar. 1, 2012.
[cited by applicant]
International Search Report and Written Opinion corresponding lo PCT Application No. PCT/US2011/065803, dated Feb. 29, 2012.
[cited by applicant]
International Search Report and Written Opinion corresponding to PCT Application No. PCT/EP2008/068167 dated Mar. 23, 2009.
[cited by applicant]
Israel Office Action issued in connection with corresponding IL Application No. 227003 on May 11, 2015.
[cited by applicant]
Jeong, et al., “Preparation of a Promising Angiogenesis PET Imaging Agent: 68Ga-Labeled c(RGDyK)-Isothiocyanatobenzyl-1,4,7-Triazacyclononane-1,4,7-Triacetic Acid and Feasibility Studies in Mice,” The Journal of Nuclear…
[cited by applicant]
Kumiko Okane et al.; “F-FDG accumulation in atherosclerosis: use of CT and MR co-registration of thoracic and carotid arteries”; Eur. J. Nuc. Med. Mal. Imaging 2006, 33; DOI 10.1007/s00259-005-0005-2; pp. 589-594.
[cited by applicant]
Kyte et al., “A Simple Method for Displaying the Hydropathic Character of a Protein”, J. Mol. Biol., vol. 157, pp. 105-132, 1982.
[cited by applicant]
Linhul T et al., Improving the tolerance of a protein a analogue to repeated alkaline exposures using a bypass mutagenesis approach, Proteins: Structure, Function, and Bioinformatics, vol. No. 55, pp. 407-416, 2004.
[cited by applicant]
Liu et al., “99mTc-Labeled Small Peptides as Diagnostic Radiopharmaceuticals”, Chemical Reviews, vol. 99, No. 9, pp. 2235-2268, 1999.
[cited by applicant]
M. Wikman et al.; “Selection and characterization of HER2/neu-binding affibody ligands”; Revision; Abstract 2Pages.
[cited by applicant]
McBride et al., Improved 18F Labeling of Peptides with a Fluoride-Aluminum-Chelate Complex, Bioconjugate Chemistry, vol. No. 21, Issue No. 7, pp. 1331-1340, 2010.
[cited by applicant]
Mume et al., “Evaluation of ((4-Hydroxyphenyl)ethyl)maleimide for Site-Specific Radiobromination of Anti-HER2 Affibody”, Bioconjugate Chem. vol. No. 16, pp. 1547-1555, 2005.
[cited by applicant]
Nilsson et al., “A synthetic IgG-binding domain based on staphylococcal protein A”, Protein Engineering, vol. 1, No. e. pp. 101-133, 1987.
[cited by applicant]
Non-Final Rejection towards related U.S. Appl. No. 13/996,109 dated Sep. 5, 2014.
[cited by applicant]
Non-Final Rejection towards related U.S. Appl. No. 13/996,142 dated Jul. 17, 2014.
[cited by applicant]
Non-Final Rejection towards related U.S. Appl. No. 13/996,142 dated Jul. 22, 2015.
[cited by applicant]
Nord et al., “Binding Proteins selected from combinatorial libraries of an alpha-helical bacterial receptor domain”, Nature Biotechnology, vol. 15, pp. 772-777, Aug. 15, 1997.
[cited by applicant]
Nygren et al., “Analysis and use of the serum albumin binding domains of streptococcal protein G”, Journal of Molecular Recognition, vol. 1, No. 2, pp. 69-74, 1988.
[cited by applicant]
Office Action issued in connection with related CN Application No. 201180068114.4 on Oct. 27, 2014.
[cited by applicant]
Office Action issued in connection with related CN Application No. 201180068115.9 on Jul. 2, 2014.
[cited by applicant]
Office Action issued in connection with related IL Application No. 226989 on May 6, 2015.
[cited by applicant]
Office Action issued in connection with related IL Application No. 226990 on May 10, 2015.
[cited by applicant]
Office Action issued in connection with related RU Application No. 2013128360 on Aug. 24, 2015.
[cited by applicant]
Office Action issued in connection with related RU Application No. 2013128361 on Aug. 24, 2015.
[cited by applicant]
Orlova et al., “Affibody Molecules for Molecular Imaging and Therapy for Cancer”, Cancer Biotherapy & RADIOPHARMACEUTICALS, vol. No. 22, Issue No. 5, pp. 573-584, 2007.
[cited by applicant]
Orlova et al., “Tumor Imaging Using a Picomolar Affinity HER2 Binding Affibody Molecule”, Cancer Research, vol. No. 66, Issue No. 8, pp. 4339-4348, Apr. 15, 2006.
[cited by applicant]
Pietras et al., “Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells”, Oncogene, vol. 9, pp. 1829-1838, 1994.
[cited by applicant]
Reichert, “Therapeutic monoclonal antibodies: Trends in development and approval in the US”, Current Opinion in Molecular Therapeutics, vol. No. 4, Issue No. 2, pp. 110-118, 2002.
[cited by applicant]
Reilly et al., “Problems of Delivery of Monoclonal Antibodies”, Pharmaceutical and Pharmacokinetic Solutions, Drug Delivery Systems, vol. 28, No. 2, pp. 126-142, 1995.
[cited by applicant]
Requirement for Restriction Election towards related U.S. Appl. No. 13/996,142 dated Apr. 24, 2014.
[cited by applicant]
Schirrmacher et al., “18F-labeling of peptides by means of an organosilicon-based fluoride acceptor”, Angew Chem. Int. Ed., vol. No. 45, pp. 6047-6050, 2006.
[cited by applicant]
Schirrmacher et al., “Synthesis of p-{Di-tert-butyl[18F]fluorosilyl)benzaldehyde {[18F]SiFA-A) with High Specific Activity by Isotopic Exchange: A Convenient Labeling Synthon for the 18F-Labeling of N-amino-oxy Derivati…
[cited by applicant]
Schneider et al., “Trastuzumab Cardiotoxicity: Speculations Regarding Pathophysiology and Targets for Further Study”, Seminars in Oncology, vol. No. 29, Issue No. 3, pp. 22-28, Jun. 2002.
[cited by applicant]
Shih et al., “Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts”, Nature, vol. 290, pp. 261-264, 1981.
[cited by applicant]
Silverman, “Human Antibody Responses to Bacterial Antigens: Studies of a Model Conventional Antigen and a Proposed Model B Cell Superantigen”, Intern. Rev. Immunol., vol. 9, pp. 57-78, 1992.
[cited by applicant]
Sjogren et al., Prognostic and Predictive Value of c-erbB-2 Overexpression in Primary Breast Cancer, Alone and in combination with other Prognostic Markers, Journal of Clinical Oncology, vol. 16, No. 2, pp. 462-469, Feb…
[cited by applicant]
Slamon et al., “Studies of the HER-21neu Proto-oncogene in Human Breast and Ovarian Cancer”, Reports, pp. 707-712, 1989.
[cited by applicant]
Sliwkowski et al., “Nonclinical Studies Addressing the Mechanism of Action of Trastuzumab (Herceptin)”, Seminars in Oncology, vol. 26, No. 4, pp. 60-70, Aug. 1999.
[cited by applicant]
Sohma et al., “O-Acyl isopeptide method for the efficient synthesis of difficult sequence-containing peptides: use of O-acyl isodipeptide unit,” Tetrahedron Letters, vol. No. 47, pp. 3013-3017, 2006.
[cited by applicant]
Sosabowski et al., “Conjugation of DOT A-like chelating agents to peptides and radiolabeling with trivalent metallic sotopes,” Nature Protocols, vol. No. 1, Issue No. 2, pp. 972-976, 2006.
[cited by applicant]
Steffen et al., “Affibody-mediated tumour targeting of HER-2 expressing xenografts in mice”, Eur J Nucl Med Mol Imaging, vol. No. 33, 631-638, Jun. 2006.
[cited by applicant]
Steffen, “Radiolabeled HER-2 Binding Affibody Molecules for Tumor Targeting”, Preclinical Studies, 2006.
[cited by applicant]
Sundaresan et al., “The Biology of Human Epidermal Growth Factor Receptor 2”, Breast Cancer, pp. 16-22, 1999.
[cited by applicant]
Thuy Tran et al.; “In Vivo Evaluation of Cysteine-Based Chelators for Attachment of 99m Tc to Tumour-Targeting Affibody Molecules”; Bioconjucate Chem. 2007, 18; Published on Web Mar. 2, 2007; pp. 549-558.
[cited by applicant]
Thuy Tran et al; “99mTc-maEEE-Z HER2:342, an Affibody Molecule Based Tracer for the Detection of HER2 Expression in Malignant Tumors”; Bioconj. Chem. 2007, 18, 1956; Published on Web Oct. 19, 2007; pp. 1956-1964.
[cited by applicant]
Tolmachev et al., “111 In-Benzyl-DTPA-ZHER2:342, an Affibody-Based Conjugate for In Vivo Imaging of HER2 Expression in Malignant Tumors”, The Journal of Nuclear Medicine, vol. No. 47, Issue No. 5, May 2006.
[cited by applicant]
Tolmachev et al., “Radionuclide Therapy of HER2-Positive Microxenografts Using a 177Lu-Labeled HER2-Specific Affibody Molecule”, Cancer Research, vol. No. 67, Issue No. 6, pp. 2773-2782, Mar. 15, 2007.
[cited by applicant]
Tolmachev, et al., “A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue,” Eur J. Nucl Med. Mol. Imaging (2010) 37:1356-1367, Feb. 4, 2010, 12 p…
[cited by applicant]
Tolmachev, et al., “Evaluation of a Maleimido Derivative of NOTA for Site-Specific Labeling of Affibody Molecules,” Bioconjugate Chemistry, ACS Publications, 2011 American Chemical Society, Bioconjugate Chem. 2011, 22, …
[cited by applicant]
Tolmachev, et al., “HEHEHE-Tagged Affibody Molecule May Be Purified by IMAC, Is Conveniently Labeled with [99mTc(CO)3)+, and Shows Improved Biodistribution with Reduced Hepatic Radioactivity Accumulation, ” Bioconjugate…
[cited by applicant]
Torun Engfeldt et al.; “Imaging Of HER2-Expressing Tumours Using A Synthetic Affibody Molecule Containing The 99mtc-Chelating Mercaptoacetyl-Glycyl-Glycyl-Glycyl(MAG3)Sequence”; Eur. J. Nucl. Med. Mal. Imaging 2007, 34;…
[cited by applicant]
Torun Engfeldt et al; “Tc-chelator engineering to improve tumour targeting properties of a HER2-specific Affibody molecule”; Eur. J. Nucl. Med. Mol. Imaging 2007, 34; pp. 1843-1853.
[cited by applicant]
Toyokuni et al, Bioconjugate Chemistry, vol. 14, pp. 1253-1259 (Year: 2003).
[cited by applicant]
Unofficial English translation of Office Action issued in connection with related JP Application No. 2013-546278 on Oct. 27, 2015.
[cited by applicant]
Unofficial English translation of Office Action issued in connection with related JP Application No. 2013-546280 on Oct. 27, 2015.
[cited by applicant]
Vaidyanathan et al., “Preparation of N-succinimidyl 3-[*I ]iodobenzoate: an agent for the indirect radioiodination of proteins,” Nature Protocols, vol. No. 1, Issue No. 2, 707-713, 2006.
[cited by applicant]
Waibel et al., “Stable one-step technetium-99m labeling of His-tagged recombiant proteins with a novel Tc(I)-carbonyl complex”, Research, Nature Biotechnology, vol. 17, pp. 897-901, 1999.
[cited by applicant]
Written Opinion issued in connection with related SG Application No. 201304772-5 on Jun. 10, 2014.
[cited by applicant]
Written Opinion issued in connection with related SG Application No. 201304883-0 dated Oct. 30, 2014.
[cited by applicant]
Korean Patent Office's Notice of Preliminary Rejection, dated Oct. 30, 2023, four pages.
[cited by applicant]